Rotation system for cell growth chamber of a cell expansion system and method of use therefor

ABSTRACT

A system and method for rotating a cell growth chamber of a cell expansion system includes a rotatable member for engaging a chamber coupling attached to the cell growth chamber. The rotatable member includes an independently operable mechanism for engaging a rotatable fitting associated with the chamber coupling. In at least one embodiment, the chamber coupling is selectively rotatable by turning the rotatable member, thereby rotating the cell growth chamber around a first axis. The cell growth chamber is also selectively rotatable around a second axis by turning the rotatable fitting associated with the chamber coupling. Other novel aspects include a way of attaching the cell growth chamber to the shaft assembly, and a new tube routing clip.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of U.S. Provisional PatentApplication No. 61/159,690 filed on Mar. 12, 2009, and U.S. ProvisionalPatent Application No. 61/153,583 filed on Feb. 18, 2009, both of whichare expressly incorporated herein by reference.

The present application cross references, but does not claim priority toU.S. patent application Ser. No. 12/042,798 (corresponding to U.S. Pat.App. Pub. No. 2008/0220523) filed on Mar. 5, 2008, the content of whichis incorporated herein by reference in its entirety.

FIELD

The present disclosure relates to a system and method for rotating acell growth chamber of a cell expansion system (CES) that is used togrow cells.

BACKGROUND

CESs are used to expand and differentiate cells. Cell expansion systemsare known in the art. For example, U.S. Pat. Nos. 5,162,225 and6,001,585 generally describe cell expansion systems designed for cellexpansion.

The potential use of stem cells in a variety of treatments and therapieshas achieved particular attention. Cell expansion systems can be used togrow stem cells, as well as other types of cells, such as bone marrowcells. Stem cells which are expanded from donor cells can be used torepair or replace damaged or defective tissues and have broad clinicalapplications for a wide range of diseases. Recent advances in theregenerative medicine field demonstrates that stem cells have propertiessuch as proliferation and self-renewal capacity, maintenance of theunspecialized state, and the ability to differentiate into specializedcells under particular conditions.

Cell expansion systems include one or more compartments for growing thecells, such as a cell growth chamber (also referred to herein as the“bioreactor”). However, a CES with a stationary cell growth chamber maylimit the production of cells as compared to a system that provides someability to adjust the position of the cell growth chamber. By way ofexample, adjusting the orientation of the cell growth chamber during apriming sequence allows the air or gas bubbles or pockets residingwithin the cell growth chamber to be driven from the cell growth chamberas the cell growth chamber is primed with a priming fluid. In addition,it is also advantageous to adjust the orientation of the cell growthchamber while cells are growing within the cell growth chamber tomitigate problems associated with cells settling within the cell growthchamber under the influence of gravity.

Accordingly, there is a need for a system of adjusting the position of acell growth chamber associated with a cell expansion system. The presentdisclosure addresses this and other needs.

SUMMARY

It is to be understood that the present invention includes a variety ofdifferent versions or embodiments, and this Summary is not meant to belimiting or all-inclusive. This Summary provides some generaldescriptions of some of the embodiments, but may also include some morespecific descriptions of other embodiments.

One or more embodiments are generally directed to a system for rotatinga cell growth chamber of a cell expansion system. More particularly, asset forth below, at least one embodiment comprises a system for rotatinga cell growth chamber about a first rotational axis and also about asecond rotational axis. Accordingly, an apparatus for rotating a cellgrowth chamber of a cell expansion system is provided, the cell growthchamber including a longitudinal axis, the apparatus comprising:

a shaft assembly including:

-   -   an outer shaft member;    -   an inner shaft member wherein at least a portion of the inner        shaft member is located radially to the interior of the outer        shaft member, wherein the outer shaft member and the inner shaft        member are substantially coaxial and share a shaft rotation        axis, the inner shaft member including a beveled pinion at a        distal end of the inner shaft member, wherein the beveled pinion        is translatable longitudinally along the shaft rotation axis,        the beveled pinion including a beveled surface;    -   a first motor for rotating the outer shaft member; and    -   a second motor for rotating the inner shaft member;

a chamber coupling connected to the cell growth chamber, the chambercoupling including a shaft fitting for detachably engaging the outershaft member, the chamber coupling including a roll collar locatedaround at least a portion of the cell growth chamber, the roll collarincluding a sloped surface for engaging the beveled pinion;

wherein when the first motor rotates the outer shaft member the cellgrowth chamber rotates around the shaft rotation axis, and wherein whenthe second motor rotates the inner shaft member the cell growth chamberrotates around the longitudinal axis of the cell growth chamber.

In at least one embodiment the beveled pinion comprises a substantiallyfrusto-conical-shaped exterior including the beveled surface forfrictionally contacting the sloped surface of the roll collar. In atleast one embodiment the beveled pinion contacts the sloped surfacealong a contact line, the contact line oriented at an oblique anglerelative to the longitudinal axis of the cell growth chamber. In atleast one embodiment the beveled pinion contacts the sloped surfacealong a contact line, wherein a bevel angle θ between the contact lineand the shaft rotation axis is substantially an inverse tangent value ofa ratio of the beveled pinion diameter to the roll collar diameter. Inat least one embodiment the inner shaft member includes a beveled pinionfitting, the beveled pinion fitting including a slotted sleeve thatslidably engages a portion of the inner shaft member. In at least oneembodiment, a pin transfers torque between the inner shaft member andthe beveled pinion fitting. Embodiments may further include a biasingmember for maintaining the beveled pinion in a distally biased position.In at least one embodiment at least one of the shaft fitting and theouter shaft member comprise an alignment guide for properly orientingthe chamber coupling for attachment to the outer shaft member. In atleast one embodiment, the shaft fitting comprises at least one springmember having a beveled distal end and a shoulder, wherein the beveleddistal end deflects upon insertion into the outer shaft member, andwherein once the shoulder clears a front edge of a receptacle of theouter shaft member, the spring member moves radially outward and causesthe shoulder to engage the front edge of the receptacle to detachablyengage the chamber coupling and the cell growth chamber to the shaftassembly.

In at least one embodiment a tubing spool is connected to the chambercoupling, and a tube routing clip is detachably attached to the tubingspool, the tube routing clip including a substantially teardrop-shapedtube routing channel for holding a section of tubing.

One or more embodiments may include one or more ways of performing aparticular function. Accordingly, an apparatus for rotating a cellgrowth chamber of a cell expansion system is provided, the cell growthchamber including a longitudinal axis, the apparatus comprising:

means for rolling the cell growth chamber around at least one of:

-   -   (a) the longitudinal axis of the cell growth chamber; and    -   (b) an axis substantially parallel to the longitudinal axis of        the cell growth chamber; and

means for pitching the cell growth chamber such that the longitudinalaxis of the cell growth chamber rotates.

In at least one embodiment, the means for rolling and the means forpitching comprise independently rotatable coaxial shaft members. In atleast one embodiment the means for rolling comprises a beveled pinionthat contacts a sloped surface of a roll collar attached to the cellgrowth chamber, and wherein when the beveled pinion rotates around arotational axis of the beveled pinion the roll collar rotates the cellgrowth chamber around the longitudinal axis of the cell growth chamber.In at least one embodiment the means for pitching comprises an outershaft member, the means for rolling comprises an inner shaft member, andat least a portion of the inner shaft member is located radially to theinterior of the outer shaft member to provide the independentlyrotatable coaxial shaft members. In at least one embodiment, a means forcoupling the cell growth chamber to the outer shaft member is provided.In at least one embodiment, the means for coupling includes a shaftfitting, the shaft fitting comprising at least one spring member havinga beveled distal end and a shoulder, wherein the beveled distal enddeflects upon insertion into the outer shaft member, and wherein oncethe shoulder clears a front edge of a receptacle of the outer shaftmember, the spring member moves radially outward and causes the shoulderto engage the front edge of the receptacle to detachably interconnectthe cell growth chamber to the outer shaft member.

In at least one embodiment the means for rolling comprises a beveledpinion that contacts a sloped surface of a roll collar attached to thecell growth chamber, wherein the beveled pinion is movable in adirection parallel to a shaft rotation axis of the outer shaft memberand the inner shaft member. In at least one embodiment the beveledpinion is biased in a longitudinally distal position by a means forbiasing. Embodiments may further include a means for transferring torquelocated between the inner shaft member and the beveled pinion. In atleast one embodiment the means for rolling comprises a beveled pinionthat contacts a sloped surface of a roll collar attached to the cellgrowth chamber, wherein the beveled pinion contacts the sloped surfacesubstantially along a contact line, and wherein the contact line isoriented at an oblique angle relative to the longitudinal axis of thecell growth chamber. In at least one embodiment the means for rollingand the means for pitching comprise independently controllable motors.

One or more embodiments are also directed at a method for rotating acell growth chamber of a cell expansion system. Accordingly, a method ofrotating a cell growth chamber of a cell expansion system around twodifferent axes is provided, wherein a first of the two axes is alongitudinal axis of the cell growth chamber, and wherein a second ofthe two axes is an axis substantially perpendicular to the longitudinalaxis of the cell growth chamber, the method comprising:

attaching a shaft fitting of a chamber coupling to an outer shaft memberof a shaft assembly; and

causing an inner shaft member located radially to the interior of theouter shaft member to rotate the cell growth chamber around thelongitudinal axis of the cell growth chamber.

In at least one embodiment the method further comprises causing theouter shaft member to rotate, thereby rotating the longitudinal axis ofthe cell growth chamber. In at least one embodiment the method furthercomprises detaching the chamber coupling from the shaft assembly byreleasing the shaft fitting and attaching a second chamber coupling tothe shaft assembly.

As used herein, “at least one,” “one or more,” and “and/or” areopen-ended expressions that are both conjunctive and disjunctive inoperation. For example, each of the expressions “at least one of A, Band C,” “at least one of A, B, or C,” “one or more of A, B, and C,” “oneor more of A, B, or C” and “A, B, and/or C” means A alone, B alone, Calone, A and B together, A and C together, B and C together, or A, B andC together.

Various embodiments of the present inventions are set forth in theattached figures and in the Detailed Description as provided herein andas embodied by the claims. It should be understood, however, that thisSummary does not contain all of the aspects and embodiments of the oneor more present inventions, is not meant to be limiting or restrictivein any manner, and that the invention(s) as disclosed herein is/are andis understood by those of ordinary skill in the art to encompass obviousimprovements and modifications thereto.

Additional advantages of the embodiments presented herein will becomereadily apparent from the following discussion, particularly when takentogether with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a front elevation view of an embodiment of a cell growthchamber;

FIG. 2 is a perspective view of a portion of a cell expansion system,including a detachably attached cell growth chamber;

FIG. 3 is a perspective view of an embodiment of a shaft assembly of thecell expansion system;

FIG. 4 is another perspective view of the shaft assembly depicted inFIG. 3;

FIG. 5 is a perspective view of the chamber coupling and the cell growthchamber;

FIG. 6 is a side elevation view of the chamber coupling and the cellgrowth chamber;

FIG. 7 is a perspective view of the shaft assembly connected to thechamber coupling that holds the cell growth chamber;

FIG. 8 is a side elevation view of the shaft assembly connected to thechamber coupling that holds the cell growth chamber;

FIG. 9 is a top plan view of the shaft assembly connected to the chambercoupling that holds the cell growth chamber;

FIG. 10 is a detailed perspective view of the distal end of the outershaft member and inner shaft member of the shaft assembly;

FIG. 11 is a cut-away perspective view of the chamber coupling whenengaged by the distal end of the inner shaft member;

FIG. 12 is a cut-away plan view of the chamber coupling when engaged bythe distal end of the inner shaft member;

FIG. 13 is cross-sectional view of the chamber coupling when engaged bythe shaft assembly;

FIG. 14 is detailed cross-sectional view of the chamber coupling whenengaged by the distal end of the inner and outer shaft members;

FIG. 15 is an exploded view of a portion of the inner shaft member;

FIG. 16 is a front elevation view of the inner and outer shaft members,including the beveled pinion;

FIGS. 17A and 17B are front elevation views of the cell growth chamberand chamber coupling when rotated in pitch mode;

FIG. 18 is a side elevation view of the cell growth chamber and chambercoupling when rotated in roll mode, wherein dashed lines indicate asecond orientation of the IC and EC inlet ports; and

FIGS. 19A-C are various views of a tube routing clip embodiment.

The drawings are not necessarily to scale.

DETAILED DESCRIPTION

The present disclosure is generally directed to a system for rotating acell growth chamber of a cell expansion system. More particularly, asset forth below, at least one embodiment comprises a system for rotatinga cell growth chamber about a first rotational axis and also about asecond rotational axis.

With reference now to FIG. 1, an example of a cell growth chamber 100 isshown in front elevation view. Cell growth chamber 100 has alongitudinal axis LA-LA and includes cell growth chamber housing 104. Inat least one embodiment, cell growth chamber housing 104 includes fouropenings or ports: IC inlet port 108, IC outlet port 120, EC inlet port128, and EC outlet port 132.

Fluid in a first circulation path enters cell growth chamber 100 throughIC inlet port 108 at a first longitudinal end 112 of the cell growthchamber 100, passes into and through the intracapillary side (referredto in various embodiments as the intracapillary (“IC”) side or “ICspace” of a hollow fiber membrane) of a plurality of hollow fibers 116,and out of cell growth chamber 100 through IC outlet port 120 located ata second longitudinal end 124 of the cell growth chamber 100. Fluid in asecond circulation path flows in the cell growth chamber 100 through ECinlet port 128, comes in contact with the extracapillary side or outside(referred to as the “EC side” or “EC space” of the membrane) of thehollow fibers 116, and exits cell growth chamber 100 via EC outlet port132. Fluid entering cell growth chamber via an EC inlet port 128 is incontact with the outside of the hollow fibers. Small molecules (e.g.water, oxygen, lactate, etc.) can diffuse through the hollow fibers fromthe interior of the hollow fiber to the EC space, or from the EC spaceto the IC space. Large molecular weight molecules such as growth factorsare typically too large to pass through the hollow fibers, and remain inthe IC space of the hollow fibers. The media may be replaced as needed.Media may also be circulated through an oxygenator to exchange gasses asneeded. Cells can be contained within the first circulation path and/orsecond circulation path, and can be on either the IC side and/or EC sideof the membrane.

Although cell growth chamber housing 104 is depicted as cylindrical inshape, it could have a variety of shapes, such as a rectangular cube.Cell growth chamber housing 104 can be made of any type of biocompatiblepolymeric material, including a substantially transparent material thatpermits an observer to see one or more of the plurality of hollow fibers116, as well as fluid residing within the cell growth chamber housing104. Various other cell growth chamber housings may differ in shape andsize.

Referring now to FIG. 2, a portion of a CES 200 is shown in perspectiveview, and includes a back portion 204 of body 208 of the CES 200. Forclarity, the front portion is not shown; however, the front portion ispreferably attached to the back portion 204, such as by hinges 212,thereby allowing the front portion to comprise a door or hatch that canbe opened to access the cell growth chamber 100 of the CES 200. Theenvironment in the vicinity of the cell growth chamber 100 istemperature controlled to provide appropriate conditions for cellgrowth.

With reference now to FIGS. 3 and 4, the shaft assembly 300 of the CES200 is shown without the cell growth chamber. The shaft assembly 300includes an outer shaft member 304 and an inner shaft member 308,wherein the inner shaft member 308 is coaxially aligned along shaftrotation axis SRA with the outer shaft member 304. In at least oneembodiment, the outer shaft member 304 includes a pair of receptacles312 (see FIG. 8) for receiving a latching element of the detachablyattachable cell growth chamber (described below). The outer shaft member304 is in contact with a bearing assembly 316 that couples the outershaft member 304 to the housing flange 320 of the back portion 204 ofbody 208. A first motor 324 is selectively operable to rotate gear 328,which in turn rotates outer shaft gear 330 that rotates the outer shaftmember 304, thereby rotating the cell growth chamber 100 in a firstrotation orientation or pitch 332 about the shaft rotation axis SRA whenthe cell growth chamber 100 is attached to the shaft assembly 300.Second motor 336 is selectively operable to rotate gear 340, which inturn rotates the inner shaft member 308, thereby rotating the cellgrowth chamber 100 in a second rotation orientation or roll 600, asdescribed below and shown in FIG. 6. Accordingly, in at least oneembodiment, the outer shaft member 304 controls the pitch 332 of thecell growth chamber, and the inner shaft member 308 controls the roll600 of the cell growth chamber 100.

Referring now to FIG. 5, a perspective view of the cell growth chamber100 is shown, wherein the cell growth chamber 100 is connected tochamber coupling 500. The chamber coupling 500 includes a chamberhousing 504 that includes a roll collar 1100 (described below), whereinthe roll collar 1100 is fixed to the cell growth chamber 100, andwherein the roll collar 1100 is rotatable within the chamber housing504. In at least one embodiment, the chamber housing 504 comprises atleast two pieces that are fastened together, such as by using a clamp,cable ties, bolts, screws and/or ultrasonically welding. Moreparticularly, the roll collar 1100 is first fixedly attached to theexterior of the cell growth chamber 100, and then the chamber housing504 is assembled over the roll collar 1100 and fastened together.

In accordance with at least one embodiment, a sample port 508 isconnected to the exterior of the chamber housing 504 of the chambercoupling 500. The sample port 508 can be used to sample fluids withinthe tubing of the CES 200. In addition, tubing spool 512 may also beattached to the chamber housing 504. The tubing spool 512 is used tohold a length of tubing (not shown) that can be sampled using a steriletubing welder during operation of the CES 200.

The position of the tubing spool 512 adjacent the cell growth chamber100 allows the tubing to be subject to the same environmental conditionsas those influencing the cell growth chamber 100. For example, thetemperature of the tubing wound around the tubing spool 512 will besubstantially the same as the temperature of the cell growth chamber. Asa result, the fluid and cell conditions in the tubing spool 512 aresubstantially identical to those within the cell growth chamber 100.Therefore, analysis of samples of fluid and cells taken from the tubingwound around the tubing spool 512 allows operators of the CES 200 tounderstand the conditions residing with the cell growth chamber 100itself.

Referring still to FIG. 5 as well as FIG. 3, in at least one embodimentthe chamber coupling 500 includes a shaft fitting 516 for mating withthe outer shaft member 304 of the shaft assembly 300. More particularly,the shaft fitting 516 includes a cylindrical male portion 520 forinsertion in a distal end 344 of the outer shaft member 304. Thecylindrical male portion 520 includes one or more spring members 524having a beveled distal end 528 and shoulder 532. The beveled distal end528 deflects upon insertion of the cylindrical male portion 520 into thedistal end 344 of the outer shaft member 304. Once the shoulder 532clears the front edge 348 of the receptacle 312 of the outer shaftmember 304, the spring member 524 moves radially outward and causes theshoulder 532 to engage the front edge 348 of the receptacle 312 toreleasably lock the chamber coupling 500 and the cell growth chamber 100to the shaft assembly 300. As those skilled in the art will appreciate,the spring member 524 requires sufficient flexibility to allow thebeveled distal end 528 to deflect inward as the cylindrical male portion520 is inserted into the distal end of 344 of the outer shaft member304, while also being sufficiently resilient to allow the beveled distalend 528 to spring back and enter the receptacle 312 of the outer shaftmember 304 such that the shoulder 532 releasably locks the chambercoupling 500 to the outer shaft member 304. In addition, in operation,spring member 524 must also maintain the engagement of the chambercoupling 500 to the shaft assembly 300 as the cell growth chamber 100 isrotated and/or otherwise manipulated. Furthermore, once the cells havebeen harvested from the cell growth chamber 100, the spring members 524must be capable of being manipulated by an operator of the CES 200 todeflect the spring members 524 radially inward until the shoulder 532clears the front edge 348 of the receptacle 312 so that the cell growthchamber 100 and its chamber coupling 500 can be pulled out and removedfrom the shaft assembly 300.

Other embodiments may comprise one or more supplemental and/oralternative engaging mechanisms to connect the chamber coupling 500 tothe outer shaft member 304. By way of example and not limitation, suchsupplemental and/or alternative engaging mechanisms may comprise athreaded coupling, one or more set screws, detents, screws, bolts,bayonet pins and/or other fasteners.

Referring now to FIG. 6, a side elevation view of the chamber coupling500 is shown. As seen in FIG. 6, in at least one embodiment thecylindrical male portion 520 comprises a pair of spring members 524,wherein the spring members 524 are positioned on opposite sides of thecylindrical male portion 520. FIG. 6 also illustrates the position ofthe second rotation orientation or roll 600, which is rotation of thecell growth chamber 100 about its longitudinal axis LA-LA (which is intothe page of FIG. 6). As used herein, “roll” is also defined as rotationof the cell growth chamber 100 such that the circumference of the cellgrowth chamber 100 is rotated about the longitudinal axis LA-LA, or anaxis substantially parallel to the longitudinal axis LA-LA. Referringnow to FIGS. 7-9, different views of the chamber coupling 500 are shownwhere the chamber coupling 500 is connected to shaft assembly 300. Moreparticularly, the shaft fitting 516 of the cylindrical male portion 520has been inserted into the distal end 344 of the outer shaft member 304of the shaft assembly 300. The beveled distal ends 528 of the springmembers 524 have been advanced in an axial direction of the outer shaftmember 304, such that the shoulders 532 of the spring members 524 haveengaged the front edge 348 of the receptacles 312.

Referring now to FIG. 10, a detail view of the distal end of the shaftassembly 300 is shown. In at least one embodiment, the outer shaftmember 304 may comprise a guide channel 1000 to serve as a guide for theinsertion of the cylindrical male portion 520 of the chamber coupling500. More particularly, guide channel 1000 is sized to receive analignment guide or guide ridge 604 (shown as a dashed line in FIG. 6)positioned along an exterior lateral side of the cylindrical maleportion 520. In use, an operator of the CES 200 aligns the guide ridge604 to correspond to the guide channel 1000, and then inserts the shaftfitting 516 into the outer shaft member 304 until the beveled distalends 528 of the spring members 524 are secured within the receptacles312 of the outer shaft member 304.

With further reference to FIG. 10, the inner shaft member 308 can beseen positioned radially interior of the outer shaft member 304. In atleast one embodiment the inner shaft member 308 is independentlyrotatable of the outer shaft member 304, such that either may beoperated separately or operated at the same time. In general, the outershaft member 304 rotates the cell growth chamber 100 in pitch mode bymoving the cell growth chamber 100 either in a clockwise or counterclockwise manner, as per arrow 332, around the shaft rotation axis SRA.

Referring still to FIG. 10 as well as FIGS. 11 and 12, the distal end1008 of the inner shaft member 308 includes structure for engaging aroll collar 1100 residing within the chamber housing 504 of the chambercoupling 500. In at least one embodiment, and as best seen in FIG. 11,the beveled surface 1020 of the beveled pinion 1012 engages the slopedsurface 1104 of the roll collar 1100. More particularly, the inner shaftmember 308 includes a beveled pinion 1012 residing at the very distalend of the inner shaft member 308, and the beveled pinion 1012 contactsthe sloped surface 1104 of the roll collar 1100 such that when the innershaft member 308 is rotated, the roll collar 1100 rotates, therebycausing the cell growth chamber 100 to rotate about its longitudinalaxis LA-LA. As seen in FIG. 12, the beveled pinion 1012 can translate inthe direction of the shaft rotation axis SRA (i.e., longitudinally alongthe axis of inner shaft member 308). This allows the beveled pinion 1012to be moved axially as the chamber coupling 500 is attached to the outershaft member 304. In so doing, the beveled surface 1020 of the beveledpinion 1012 is placed in contact with the sloped surface 1104 of theroll collar 1100 so that when the inner shaft member 308 is rotated, therotation the inner shaft member 308 causes the roll collar 1100 torotate the cell growth chamber 100 about its longitudinal axis LA-LA.The coil spring 1460 (discussed in detail below) acts as a biasingmember to force the beveled surface 1020 to contact the sloped surface1104 of the roll collar 1100. The beveled pinion 1012 may move axiallyin the direction of arrow 1200 back and forth when a chamber coupling500 is attached and removed from the shaft assembly 300. Accordingly,the beveled pinion 1012 may move approximately 0.1 to 0.5 inchesaxially, and more preferably, approximately 0.2 to 0.4 inches axially,and more preferably yet, approximately 0.25 to 0.375 inches axially whenthe chamber coupling 500 is attached to the outer shaft member 304,thereby axially displacing the beveled pinion 1012 as the beveledsurface 1020 seats and makes contact against the sloped surface 1104 ofthe roll collar 1100.

To achieve the rotation of the roll collar 1100, in at least oneembodiment the beveled pinion 1012 includes a feature for frictionallyengaging a sloped surface 1104 of the roll collar 1100. By way ofexample and not limitation, the beveled pinion 1012 may include aplurality of ribs 1016, such as thirty-two ribs per inch of thecircumferential length of the beveled surface 1020 of the beveled pinion1012. The sloped surface 1104 of the roll collar 1100 may also include aplurality of ribs 1108, wherein the ribs 1016 of the beveled surface1020 of the beveled pinion 1012 engage the troughs between the ribs 1108of the sloped surface 1104 of the roll collar 1100. Those skilled in theart will appreciate that the beveled surface 1020 may includealternative or different surficial features, such as texturing, gearteeth, and/or another type of feature for promoting frictionalengagement between the beveled surface 1020 of the beveled pinion 1012and the sloped surface 1104 of the roll collar 1100. In at least oneembodiment, the beveled surface 1020 of the beveled pinion 1012 and/orthe sloped surface 1104 of the roll collar 1100 comprise an elastomericmaterial.

Referring now to FIG. 13, a cross-sectional view of the shaft assembly300 engaging the chamber coupling 500 with the cell growth chamber 100is shown. FIG. 13 illustrates that there is a first plurality ofbearings 316 to rotationally isolate the outer shaft member 304 from thehousing flange 320, as well as a second radially interior plurality ofbearings 1300 to rotationally isolate the outer shaft member 304 fromthe inner shaft member 308.

With reference now to FIG. 14, a detailed cross-sectional view of thedistal end of the shaft assembly 300 is illustrated engaging the chambercoupling 500. To further aid in illustrating the distal end of the shaftassembly 300, an exploded view of the distal end 1008 of the inner shaftmember 308 is shown in FIG. 15. In at least one embodiment, the distalend 1008 of the inner shaft member 308 includes a receiving portion 1400that further includes a first diameter portion 1404 and a seconddiameter portion 1408, wherein a diameter D1 of the of the firstdiameter portion 1404 is greater than a diameter D2 of the seconddiameter portion 1408. A beveled pinion fitting 1412 is detachablyattached to the second diameter portion 1408. The beveled pinion fitting1412 includes a slotted sleeve 1416 for slidably engaging the seconddiameter portion 1408 in a longitudinal orientation. The beveled pinionfitting 1412 includes the beveled pinion 1012 and the slotted sleeve1416, that together may comprise a single integral piece. Alternatively,a backer ring 1420 and nut 1424 may be used to secure the beveled pinion1012 to the slotted sleeve 1416.

As noted above, the slotted sleeve 1416 slidably engages the seconddiameter portion 1408. The beveled pinion fitting 1412 is held inslidable engagement with the second diameter portion 1408 by a fastener,such as a bolt or screw 1428, that threads into aperture 1432. A flatwasher 1436 contacts the distal face 1440 of the second diameter portion1408. In addition, the flat washer 1436 serves to limit the longitudinaldistal movement of the beveled pinion fitting 1412, and thus, thebeveled pinion 1012, by blocking the longitudinal distal movement of theinner flange 1444 of the beveled pinion fitting 1412. The inner flange1444 of the beveled pinion fitting 1412 can best be seen in FIGS. 14 and16. A lock washer or star washer 1446 may be used between the flatwasher 1436 and the screw 1428 to prevent the screw 1428 from backingout of the aperture 1432.

Referring now to FIGS. 14 and 15, a pin 1448 serves to transfer thetorque from the inner shaft member 308 to the beveled pinion fitting1412. More particularly, the pin 1448 resides within and extendsradially beyond an aperture 1452, wherein an aperture axis AA-AA of theaperture 1452 is situated substantially perpendicular to the shaftrotational axis SRA. Accordingly, the pin has a length L, where L isgreater than the diameter D2 of the second diameter portion 1408. Whenthe inner shaft member 308 is rotated, a circumferential surface 1500 ofthe pin 1448 contacts a slot surface 1504 of a slot 1508 located in theslotted sleeve 1416 of the beveled pinion fitting 1412. In so doing,when the inner shaft member 308 is rotated, the pin 1448 transfers thetorque to the slotted sleeve 1416, thereby causing the beveled pinion1012 to rotate about its axis. The beveled pinion fitting 1412 is ableto move in a proximal longitudinal direction along the second diameterportion 1408 because the ends of the pin 1448 reside within slot 1508.

To maintain the beveled pinion 1012 in contact with the roll collar 1100of the chamber coupling 500, a back shoulder 1456 of the backer ring1420 engages a distal end 1512 of a biasing member, such as coil spring1460. Of course, if the backer ring 1420, nut 1424 and beveled pinion1012 are an integral piece collectively with the slotted sleeve 1416,then the beveled pinion 1012 may include a back shoulder or similarstructure for engaging the distal end 1512 of the coil spring 1460. Asbest seen in FIG. 14, one or more spacer rings 1464 may be used betweenthe proximal end of the coil spring 1460 and the body of the inner shaftmember 308 to adjust the force of the coil spring 1460 acting on thebeveled pinion 1012. The coil spring 1460 serves to maintain the beveledpinion fitting 1412, and thus, the beveled pinion 1012, in a biaseddistal position so that the beveled pinion 1012 engages the roll collar1100 to rotate the cell growth chamber 100 about its longitudinal axisLA-LA.

The longitudinal extent of movement of the beveled pinion fitting 1412in the distal direction is limited by the inner flange 1444 of thebeveled pinion fitting 1412 contacting the flat washer 1436. Thelongitudinal extent of movement of the beveled pinion fitting 1412 inthe proximal direction is limited by the pin 1448 contacting a distalend 1516 of the slot 1508 residing within the slotted sleeve 1416.

Referring still to FIG. 14, the beveled surface 1020 of the beveledpinion 1012 contacts the sloped surface 1104 of the roll collar 1100along contact line 1468. The orientation of the contact line 1468intercepts the longitudinal axis LA-LA of the cell growth chamber 100 atan oblique angle. The bevel angle 13, defined as the angle formedbetween the shaft rotation axis SRA and the contact line 1468, is theinverse tangent of the ratio of the beveled pinion 1012 and the rollcollar 1100 diameters, the diameters being measured at some point on thecontact line 1468.

With reference now to FIGS. 17A and 17B, an example of rotating the cellgrowth chamber in the pitch mode is illustrated. In FIG. 17A, thelongitudinal axis LA-LA is substantially horizontal, and in FIG. 17B,the longitudinal axis LA-LA is substantially vertical. It is to beunderstood that the pitch 332 of the cell growth chamber 100 can beselectively controlled such that the longitudinal axis LA-LA is rotatedat any angle. That is, the longitudinal axis LA-LA of the cell growthchamber 100 can be rotated such that it is oriented at any angle θ to360 degrees. For example, the longitudinal axis LA-LA can be oriented 45degrees clockwise of vertical, or 60 degrees counter-clockwise ofvertical. At a minimum, rotation of the cell growth chamber 100 in pitchmode assists in directing air or gas bubbles toward one or both of theIC outlet port 120 or EC outlet port 132 as the cell growth chamber 100is being filled with a priming fluid in preparation for loading cells inthe cell expansion system 200.

With reference now to FIG. 18, an example of rotating the cell growthchamber in the roll mode is illustrated. In FIG. 18, a side elevationview of the cell growth chamber 100 is shown, wherein in a first rollposition (shown with solid lines), the EC inlet port 128 is orientedvertically upwards. In a second roll position (shown with dashed lines),the EC inlet port 128 is oriented downwards. It is to be understood thatthe roll 600 of the cell growth chamber 100 can be selectivelycontrolled such that the cell growth chamber 100 can be rotated at anyangle around its longitudinal axis. Periodic rotation of the cell growthchamber 100 assists in preventing colonies of cells from settling duringthe cell expansion process.

As those skilled in the art will appreciate, roll can be achieved byrotating the cell growth chamber around its longitudinal axis.Alternatively, roll may be achieved differently, such as by rotating ahinged arm that swings the cell growth chamber 100 from a first verticalupward position to a second vertical downward position (or any angle inbetween such positions). For such a configuration, the cell growthchamber rotates about an axis substantially parallel to the longitudinalaxis of the cell growth chamber. The arm could then be tilted left orright to pitch the cell growth chamber. Thus, alternative ways ofachieving pitch and roll are possible and are encompassed by the presentdisclosure.

In a separate embodiment, various views of a tube routing clip 1900 areshown in FIGS. 19A-C. The tube routing clip 1900 is used to provide adetachably attachable device with a sufficient radius of curvature forbending the tubing associated with the CES 200 without causing thetubing damage. More particularly, while the tubing spool 512 provides alength of tubing that can be sampled using a sterile tubing welderduring operation of the CES 200, once the tubing has been cut andwelded, the welds of the tubing are prone to kinking if bent in arelatively small radius. Accordingly, the tube routing clip 1900 allowsthe tubing to be turned in a 180 degree direction without causing thewelds in the tubing to kink.

Referring still to FIGS. 19A-C, the tube routing clip 1900 includes asubstantially teardrop-shaped body 1904. The perimeter of the body 1904includes a routing channel 1908 for receiving the tubing T (shown inFIG. 19B only). The rear portion 1912 of the body 1904 includes a pairof C-shaped tubing receptacles 1916 that are sized for receiving andholding the tubing once the tubing is pushed into the pair of C-shapedtubing receptacles 1916. The front portion 1920 of the body 1904includes a pair of spring clips 1924 for engaging the tubing spool 512.FIG. 5 illustrates the tube routing clip 1900 attached to the perimeterof the tubing spool 512.

In use, an operator of the CES 200 may periodically be tasked withobtaining a sample of the cells being grown in the cell growth chamber100. The operator can remove a fluid-filled section of the tubing fromthe tubing spool 512 by using a sterile tubing welder. The length of thetubing remaining on the tubing spool 512 then includes a weld. Theoperator can place the tubing T with the weld W along the routingchannel 1908 without causing a kink, wrinkle or blockage in the tubing.The spring clips 1924 allow the tube routing clip 1900 to be detachedand reattached as may be needed to access the tubing held on the tubingspool 512, and to facilitate ease of manipulation of the tubing so thatthe weld W can be properly positioned along the routing channel 1908prior to reattaching the routing clip 1900 to the tubing spool 512.

Various components may be referred to herein as “operably associated.”As used herein, “operably associated” refers to components that arelinked together in operable fashion, and encompasses embodiments inwhich components are linked directly, as well as embodiments in whichadditional components are placed between the two linked components.

The one or more present inventions may be embodied in other specificforms without departing from its spirit or essential characteristics.The described embodiments are to be considered in all respects only asillustrative and not restrictive. The scope of the invention is,therefore, indicated by the appended claims rather than by the foregoingdescription. All changes which come within the meaning and range ofequivalency of the claims are to be embraced within their scope.

The one or more present inventions, in various embodiments, includecomponents, methods, processes, systems and/or apparatus substantiallyas depicted and described herein, including various embodiments,subcombinations, and subsets thereof. Those of skill in the art willunderstand how to make and use the present invention after understandingthe present disclosure.

The one or more present inventions, in various embodiments, includeproviding devices and processes in the absence of items not depictedand/or described herein or in various embodiments hereof, including inthe absence of such items as may have been used in previous devices orprocesses (e.g., for improving performance, achieving ease and/orreducing cost of implementation).

The foregoing discussion of the one or more present inventions has beenpresented for purposes of illustration and description. The foregoing isnot intended to limit the one or more present inventions to the form orforms disclosed herein. In the foregoing Detailed Description forexample, various features of the one or more present inventions aregrouped together in one or more embodiments for the purpose ofstreamlining the disclosure. This method of disclosure is not to beinterpreted as reflecting an intention that the claimed inventionrequires more features than are expressly recited in each claim. Rather,as the following claims reflect, inventive aspects lie in less than allfeatures of a single foregoing disclosed embodiment. Thus, the followingclaims are hereby incorporated into this Detailed Description, with eachclaim standing on its own as a separate preferred embodiment of the oneor more present inventions.

Moreover, though the description of the one or more present inventionshas included description of one or more embodiments and certainvariations and modifications, other variations and modifications arewithin the scope of the invention (e.g., as may be within the skill andknowledge of those in the art, after understanding the presentdisclosure). It is intended to obtain rights which include alternativeembodiments to the extent permitted, including alternate,interchangeable and/or equivalent structures, functions, ranges or stepsto those claimed, whether or not such alternate, interchangeable and/orequivalent structures, functions, ranges or steps are disclosed herein,and without intending to publicly dedicate any patentable subjectmatter.

1. An apparatus for rotating a cell growth chamber of a cell expansionsystem, the cell growth chamber including a longitudinal axis, theapparatus comprising: a shaft assembly including: an outer shaft member;an inner shaft member wherein at least a portion of the inner shaftmember is located radially to an interior of the outer shaft member,wherein the outer shaft member and the inner shaft member aresubstantially coaxial and share a shaft rotation axis, the inner shaftmember including a beveled pinion at a distal end of the inner shaftmember, wherein the beveled pinion is translatable longitudinally alongthe shaft rotation axis, the beveled pinion including a beveled surface;a first motor for rotating the outer shaft member; and a second motorfor rotating the inner shaft member; a chamber coupling connected to thecell growth chamber, the chamber coupling including a shaft fitting fordetachably engaging the outer shaft member, the chamber couplingincluding a roll collar located around at least a portion of the cellgrowth chamber, the roll collar including a sloped surface for engagingthe beveled pinion; wherein when the first motor rotates the outer shaftmember the cell growth chamber rotates around the shaft rotation axis,and wherein when the second motor rotates the inner shaft member thecell growth chamber rotates around the longitudinal axis of the cellgrowth chamber.
 2. The apparatus of claim 1, wherein the beveled pinioncomprises a substantially frusto-conical-shaped exterior including asurface for frictionally contacting the sloped surface of the rollcollar.
 3. The apparatus of claim 1, wherein the beveled pinion contactsthe sloped surface along a contact line, the contact line oriented at anoblique angle relative to the longitudinal axis of the cell growthchamber.
 4. The apparatus of claim 1, wherein the beveled pinioncontacts the sloped surface along a contact line, and wherein a bevelangle β between the contact line and the shaft rotation axis issubstantially an inverse tangent value of a ratio of a beveled piniondiameter to a roll collar diameter.
 5. The apparatus of claim 1, whereinthe inner shaft member includes a beveled pinion fitting, the beveledpinion fitting including a slotted sleeve that slidably engages aportion of the inner shaft member.
 6. The apparatus of claim 5, whereina pin transfers torque between the inner shaft member and the beveledpinion fitting.
 7. The apparatus of claim 5, further comprising abiasing member for maintaining the beveled pinion in a distally biasedposition.
 8. The apparatus of claim 1, wherein at least one of the shaftfitting and the outer shaft member comprise an alignment guide forproperly orienting the chamber coupling for attachment to the outershaft member.
 9. The apparatus of claim 1, wherein the shaft fittingcomprises at least one spring member having a beveled distal end and ashoulder, wherein the beveled distal end deflects upon insertion intothe outer shaft member, and wherein once the shoulder clears a frontedge of a receptacle of the outer shaft member, the at least one springmember moves radially outward and causes the shoulder to engage thefront edge of the receptacle to detachably engage the chamber couplingand the cell growth chamber to the shaft assembly.
 10. The apparatus ofclaim 1, wherein a tubing spool is connected to the chamber coupling,and wherein a tube routing clip is detachably attached to the tubingspool, the tube routing clip including a substantially teardrop-shapedtube routing channel for holding a section of tubing.